1. Field of the Invention
The present invention relates to an adhesive preparation that is applied in the mouth and used upon administration of a medicine in the mouth. Further, the present invention relates to an oral adhesive sheet and more particularly to an oral adhesive sheet including a separator and a plurality of sections mounted on the separator, having a pressure-sensitive adhesive layer containing a medicine for adhering to the oral mucous membrane such as gingival mucous membrane so as to apply the medicine through the mucous membrane to improve handling property of the adhesive sheet.
2. Description of the Related Art
Heretofore, various methods have been known for the administration of medicines in the mouth. For example, there have been known methods using solution, ointment, jelly, spray, troche, buccal tablet, sublingual tablet, etc., respectively.
Recently, as a preparation that has good adhesiveness even in an oral cavity mucous membrane wetted with moisture such as saliva, there has been proposed an oral adhesive preparation having a pressure-sensitive adhesive layer containing a medicine, a base (major component) of the pressure-sensitive adhesive layer comprising a water soluble or water swellable polymer. For example, a mucous membrane-adhering preparation having a substrate and a mucous membrane adhering pressure-sensitive adhesive layer on the substrate, containing an alginic acid ester and a medicine (JP-A-61-30516), an external film preparation containing hydroxypropyl cellulose as a major component and a pharmaceutical preparation (JP-A-62-63513), local anesthetic adhesive preparation for application to gingiva, having a pressure-sensitive adhesive layer comprising a water-soluble polymer such as polyvinylpyrrolidone and a water-insoluble or water-swellable polymeric substance such as polyvinyl acetate and a physiologically active component (JP-A-1-272521), an oral application substrate of a two-layer structure produced by casting and drying a liquid containing a polyacrylic acid salt, a carboxyvinyl polymer and polyvinyl alcohol (JP-A-5-310561), etc.
In the case of the conventional oral adhesive preparations containing water-soluble or water-swellable polymer as a basis (major component) of the adhesive layer, the water-soluble or water-swellable polymer absorbs the moisture present on the surface of adherent (surface of the mucous membrane in the oral cavity). This causes the surface of the adhesive layer to contact the surface of the adherent to effect adhesion.
As means for administering a medicine through the mucous membrane, there have been developed sheet-form adhesive preparation having good adhesion (pressure-sensitive adhesion) even at wetted site. Many attempts from the viewpoint of composition have been made on such a sheet-form adhesive preparation. For example, adhesive preparations are designed to use a water-soluble or water-swellable polymer as a basis for adhesive in order to impart adhesiveness to the wetted site.
On the other hand, as means for administering a medicine through skin, there have been developed and widely used various endermic pharmaceutical preparations using pressure-sensitive adhesives. Such endermic pharmaceutical preparations include various forms. As typical examples, mention is made of adhesive sheet-type adhesive preparations having a non-water-soluble pressure-sensitive adhesive layer containing a medicine and a support layer. These types of adhesive preparations have not been used as an oral adhesive preparation. This is because it has been recognized that the non-water-soluble pressure-sensitive adhesive layer generally shows no sufficient adhesion to an adherent that is wetted with moisture.
However, it sometimes occurs that such an oral adhesive preparation is detached and removed due to the swelling or dissolution of the water-soluble or water-swelling polymer in the adhesive layer with water or that the medicine seeps and flows away from the adhesive layer. When the adhesive layer deforms to a large extent as a result of the swelling of a water-swellable polymer, the user will feel the existence of foreign body in the mouth. In case where no such problem as detachment or falling off does occur, generally adhesion with a strong adhesive strength occurs so that when it is attempted to detach the dressing preparation in a short time (that is, it is attempted to detach it quickly), pain is accompanied or there is the danger that the mucous membrane in the mouth is damaged.
Further, when a sheet-form adhesive preparation is applied into the mouth, adhesive preparation for oral application, in particular one for application to gingival mucous membrane are used in the form of small sections (application sections) of 1 cmxc3x971 cm since the area at the site of application is small as compared with the area of external skin surface. Generally, the adhesive preparation for oral application must have pharmacological effects, acceptable application feeling, adhesion, etc. In addition, in the field of medical treatment, for example, when surface anesthesia is performed in the region of dentistry, the property of easy handling upon its application is also important so that the form of product is also one of the important elements. For this reason, a product having a product form that is easy to handle in the field of therapy is desired.
Under the circumstances, an object of the present invention is to provide an oral adhesive preparation that adheres to the oral mucous membrane with an adhesive strength agreeable to adhesion in the oral cavity, that causes no detachment or falling off or seeping or flowing away of the medicine, that gives substantially no foreign feeling upon application and that can be readily detached in a short time.
Another object of the present invention is to provide an adhesive preparation used by applying in oral cavity that is of a form such that it can be used effectively in view of easy handling in the field of therapy.
As a result of intensive research, the present inventors have found that a hydrophobic pressure-sensitive adhesive layer, that is, a pressure-sensitive adhesive layer that is substantially insoluble in water (non-water-soluble pressure-sensitive adhesive) or a pressure-sensitive adhesive layer that absorbs substantially no water is difficult to adhere to an adherent when water is present on the surface of the adherent in such a large amount that the water behaves as a fluid but it can adhere to the surface of the adherent by removing the fluid water that is present on the surface of the adherent in a large amount to such an extent that the surface of the adherent is wetted with moisture more or less.
Furthermore, the present inventors have found that mounting a plurality of sections each comprising a pressure-sensitive adhesive layer containing a medicine and a substrate on a separator generally square in shape in a specified arrangement or pattern gives rise to an adhesive sheet having an excellent handling property. The present invention has been accomplished based on the above discoveries.
Therefore, the present invention provide the followings:
1) An oral adhesive preparation comprising a substrate and a pressure-sensitive adhesive layer provided on at least one surface of the substrate, wherein the pressure-sensitive adhesive layer contains a medicine, and is substantially insoluble in water or absorbs substantially no water.
2) The oral adhesive preparation as described in 1 above, wherein the substrate comprises a non-woven fabric that has a basis weight of 20 to 150 g/m2 as prescribed in JIS-L1085 and a thickness of 0.1 to 1.0 mm as prescribed in JIS-L1085.
3) The oral adhesive preparation as described in 2 above, wherein the non-woven fabric has a bending resistance (45xc2x0 cantilever method) of 10 to 80 mm as prescribed in JIS-L1085.
4) The oral adhesive preparation as described in 2 above, wherein the non-woven fabric comprises as a major component at least one of polyolefin fiber and polyester fiber.
5) The oral adhesive preparation as described in 2 above, wherein the non-woven fabric is spun lace non-woven fabric.
6) The oral adhesive preparation as described in 1 above, wherein a combination of the pressure-sensitive adhesive layer that contains a medicine and the substrate has a bending resistance (450 cantilever method) of 15 to 60 mm as prescribed in JIS-L1085.
7) The oral adhesive preparation as described in 1 above, wherein the pressure-sensitive adhesive layer that is substantially insoluble in water or absorbs substantially no water comprises at least one member selected from the group consisting of acrylic-based polymers, rubber-based adhesives, silicone-based adhesives, vinyl ether-based adhesives, and vinyl ester-based adhesives.
8) The oral adhesive preparation as described in 7 above, wherein the adhesive comprising an acrylic-based polymer is a copolymer of (meth)acrylic acid alkyl ester and (meth)acrylic acid.
9) The oral adhesive preparation as described in 1 above, wherein the copolymer of (meth)acrylic acid alkyl ester and (meth) acrylic acid comprises a copolymer of 65 to 99% by weight of (meth)acrylic alkyl ester and 1 to 35% by weight of (meth)acrylic acid.
10) The oral adhesive preparation as described in 1 above, wherein the medicine is a local anesthesia.
11) The oral adhesive preparation as described in 10 above, wherein the local anesthesia is at least one member selected from the group consisting of lidocaine, cocaine, procaine, chloroprocaine, tetracaine, benzocaine, mepivacaine, prilocaine, bupivacaine, dibucaine, propoxycaine, etidocaine, dichlonine, and pharmacologically acceptable salts thereof.
12) The oral adhesive preparation as described in 1 above, wherein the medicine is a systemic medicine.
13) The oral adhesive preparation as described in 12 above, wherein the systemic medicine is at least one member selected from the group consisting of corticosteroids, analgesic antiphlogistics, narcotic sedatives, tranquilizers, antihypertensives, hypotensive diuretics, antibiotics, systemic anesthesia, antibacterial agents, antifungal agents, vitamins, coronary vessel dilators, antihistamines, expectorants, sex hormones, antidepressants, brain circulation improvers, antiemetics, antineoplastics, antiulcers, and biomedicines.
14) An oral adhesive sheet comprising a separator release-treated on one or both surfaces thereof and a plurality of sections for application to oral mucous membrane mounted on at least one surface of the separator, wherein the sections comprise each a flexible support and a pressure-sensitive adhesive layer on one surface of the substrate, wherein the sections are adhered and arranged on the separator in 2 to 5 columns by 2 to 5 arrows, each section being in a substantially equivalent distance from adjacent section, and wherein inter-section distance between any adjacent two sections is set such that a proportion of a minimum inner diameter, Dp, of an incircle passing a center of gravity, W, of a section to a shortest distance, Di, of an adjacent section is 1.5 to 6.
15) The oral adhesive sheet as described in 14 above, wherein the substrate is cloth.
16) The oral adhesive sheet as described in 14 above, wherein the medicine is a local anesthetic.
17) The oral adhesive sheet as described in 14 above, wherein the sheet shows an angle of deflection of 10 degrees or less when held horizontally at a prehension width of 5 mm at one of two points on a peripheral portion of the separator defining a largest linear length.
18) The oral adhesive sheet as described in 14 above, wherein the section is a section for application to gingival mucous membrane.
19) The oral adhesive sheet as described in 14 above, wherein the section is a section as described in 1 above.
The oral adhesive preparation of the present invention can adhere to the mucous membrane in the oral cavity with moderate adhesive force and can be readily detached in a short time. In particular, it can administer a drug efficiently without causing falling-off of the adhesive layer or seeping or flowing away of the drug, and gives no feeling of non-self or foreign feeling so that it is practically very useful.
Since the oral adhesive sheet has the above-described construction, it is excellent in handling property upon detaching the sections from the separator. At t the same time, because of the arrangement of sections having each a suitable size mounted in a number required for in the field of actual therapy, a reduction in operation time for the therapy can be expected. Further, the proportion of the size of each section to the inter-section distance set to specific values increases processability upon production to thereby increase productivity.
The above and other objects, effects, features and advantages of the present invention will become more apparent from the following description of preferred embodiments.